PMID- 22526674
OWN - NLM
STAT- MEDLINE
DCOM- 20120824
LR  - 20211216
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 80
IP  - 7
DP  - 2012 Jul
TI  - The A subunit of Escherichia coli heat-labile enterotoxin functions as a mucosal 
      adjuvant and promotes IgG2a, IgA, and Th17 responses to vaccine antigens.
PG  - 2426-35
LID - 10.1128/IAI.00181-12 [doi]
AB  - Enterotoxigenic Escherichia coli (ETEC) produces both heat-labile (LT) and 
      heat-stable (ST) enterotoxins and is a major cause of diarrhea in infants in 
      developing countries and in travelers to those regions. In addition to inducing 
      fluid secretion, LT is a powerful mucosal adjuvant capable of promoting immune 
      responses to coadministered antigens. In this study, we examined purified A 
      subunit to further understand the toxicity and adjuvanticity of LT. Purified A 
      subunit was enzymatically active but sensitive to proteolytic degradation and 
      unable to bind gangliosides, and even in the presence of admixed B subunit, it 
      displayed low cyclic AMP (cAMP) induction and no enterotoxicity. Thus, the AB5 
      structure plays a key role in protecting the A subunit from proteolytic 
      degradation and in delivering the enzymatic signals required for secretion. In 
      contrast, the A subunit alone was capable of activating dendritic cells and 
      enhanced immune responses to multiple antigens following intranasal immunization; 
      therefore, unlike toxicity, LT adjuvanticity is not dependent on the AB5 
      holotoxin structure or the presence of the B subunit. However, immune responses 
      were maximal when signals were received from both subunits either in an AB5 
      structure or with A and B admixed. Furthermore, the quality of the immune 
      response (i.e., IgG1/IgG2 balance and mucosal IgA and IL-17 secretion) was 
      determined by the presence of an A subunit, revealing for the first time 
      induction of Th17 responses with the A subunit alone. These results have 
      important implications for understanding ETEC pathogenesis, unraveling 
      immunologic responses induced by LT-based adjuvants, and developing new mucosal 
      vaccines.
FAU - Norton, Elizabeth B
AU  - Norton EB
AD  - Department of Microbiology and Immunology, Tulane University School of Medicine, 
      New Orleans, Louisiana, USA.
FAU - Lawson, Louise B
AU  - Lawson LB
FAU - Mahdi, Zaid
AU  - Mahdi Z
FAU - Freytag, Lucy C
AU  - Freytag LC
FAU - Clements, John D
AU  - Clements JD
LA  - eng
GR  - R01 EB006493/EB/NIBIB NIH HHS/United States
GR  - EB006493-04/EB/NIBIB NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120423
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Enterotoxins)
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Protein Subunits)
RN  - 0 (Vaccines)
RN  - D9K3SN2LNY (heat-labile enterotoxin, E coli)
SB  - IM
MH  - Adjuvants, Immunologic/*administration & dosage/adverse effects
MH  - Administration, Intranasal
MH  - Animals
MH  - Bacterial Toxins/*administration & dosage/adverse effects
MH  - Dendritic Cells/immunology
MH  - Enterotoxins/*administration & dosage/adverse effects
MH  - Escherichia coli Proteins/*administration & dosage/adverse effects
MH  - Immunoglobulin A/*immunology
MH  - Immunoglobulin G/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Protein Subunits/administration & dosage
MH  - Th17 Cells/*immunology
MH  - Vaccines/administration & dosage/adverse effects/*immunology
PMC - PMC3416479
EDAT- 2012/04/25 06:00
MHDA- 2012/08/25 06:00
PMCR- 2013/01/01
CRDT- 2012/04/25 06:00
PHST- 2012/04/25 06:00 [entrez]
PHST- 2012/04/25 06:00 [pubmed]
PHST- 2012/08/25 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - IAI.00181-12 [pii]
AID - 00181-12 [pii]
AID - 10.1128/IAI.00181-12 [doi]
PST - ppublish
SO  - Infect Immun. 2012 Jul;80(7):2426-35. doi: 10.1128/IAI.00181-12. Epub 2012 Apr 
      23.